[Classification, diagnosis and treatment status of pulmonary hypertension from 2012 to 2019: a single center study in Yunnan province].

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.

Signature of spin-phonon coupling driven charge density wave in a kagome magnet.

The intertwining between spin, charge, and lattice degrees of freedom can give rise to unusual macroscopic quantum states, including high-temperature superconductivity and quantum anomalous Hall effects. Recently, a charge density wave (CDW) has been observed in the kagome antiferromagnet FeGe, indicative of possible intertwining physics. An outstanding question is that whether magnetic correlation is fundamental for the spontaneous spatial symmetry breaking orders. Here, utilizing elastic and high-resolution inelastic x-ray scattering, we observe a c-axis superlattice vector that coexists with the 2[Formula: see text]2[Formula: see text]1 CDW vectors in the kagome plane. Most interestingly, between the magnetic and CDW transition temperatures, the phonon dynamical structure factor shows a giant phonon-energy hardening and a substantial phonon linewidth broadening near the c-axis wavevectors, both signaling the spin-phonon coupling. By first principles and model calculations, we show that both the static spin polarization and dynamic spin excitations intertwine with the phonon to drive the spatial symmetry breaking in FeGe.

[Clinical observation of bow-tie adjustable suture technique for overcorrection in intermittent exotropia].

Objective: To investigate the clinical effects of the bow-tie adjustable suture technique in managing overcorrection in patients with intermittent exotropia after surgery. Methods: This was a retrospective case series study. Clinical data were collected from children with intermittent exotropia who underwent strabismus correction surgery, including the bow-tie adjustable suture technique and conventional techniques, at the Department of Strabismus and Pediatric Ophthalmology, Shanxi Eye Hospital, from January 2020 to September 2021. Children with postoperative esodeviation≥15 prism diopters (PD) within the first 6 days were treated differently based on the surgical technique and their individual conditions, including suture adjustment and conservative treatment. The overcorrection rate and its changes among different surgical groups, the recovery of ocular alignment and binocular visual function after different treatment methods in children with overcorrection on the sixth postoperative day, and the postoperative complications in different surgical groups were observed. Statistical analysis was performed using independent samples t-test, Wilcoxon rank-sum test, repeated-measures analysis of variance, Bonferroni test, chi-square test, or Fisher's exact probability test, as appropriate. Results: A total of 643 children who underwent intermittent exotropia correction surgery were included in the study. Among them, 325 children underwent the bow-tie adjustable suture technique, with 185 males and 140 females, and the mean age was (9.50±2.69) years. The remaining 318 children underwent conventional techniques, with 176 males and 142 females, and the mean age was (9.90±2.67) years. There were no statistically significant differences in age and gender distribution between the two surgical groups (all P>0.05). On the first postoperative day, among children who underwent the bow-tie adjustable suture technique, 40 had an esodeviation of≥10 PD, resulting in an overcorrection rate of 12.3% (40/325), while among children who underwent conventional techniques, 32 had an esodeviation of≥10 PD, resulting in an overcorrection rate of 10.1% (32/318). On the sixth postoperative day, these rates decreased to 5.5% (18/325) and 3.1% (10/318) in the two groups, respectively. At 1, 6, and 12 months postoperatively, the overcorrection rate in children who underwent the bow-tie adjustable suture technique was 0, while in children who underwent conventional techniques, the overcorrection rate did not show a significant decrease compared to before surgery. The differences between the two surgical groups were statistically significant (all P<0.05). On the sixth postoperative day, among children with an esodeviation of≥15 PD, 13 underwent suture adjustment and 7 received conservative treatment. The results of repeated-measures analysis of variance showed statistically significant differences in near and distance esodeviation angles among children who received different treatment methods (F=145.20, 106.87, both P<0.001), as well as statistically significant differences in near and distance esodeviation angles at different time points within each group of children (F=81.67, 35.09, both P<0.001). There were also significant differences in the trends of change in near and distance esodeviation angles at different time points among children who received different treatment methods (F=79.90, 36.73, both P<0.001). Further pairwise comparisons showed significant differences in near and distance esodeviation angles between the sixth postoperative day and 1, 6, and 12 months postoperatively in children who underwent suture adjustment (all P<0.05), while no statistically significant differences were observed in children who received conservative treatment (all P>0.05). At 12 months postoperatively, among the 13 children who underwent suture adjustment, 12 achieved stereopsis, while among the 7 children who received conservative treatment, all became stereo-blind after removing the prismatic correction. No serious complications occurred in any of the children postoperatively. Conclusion: The proportion of children with intermittent exotropia who achieved orthotropic alignment one year after surgery was relatively low among those who had an overcorrection of≥15 PD on the sixth postoperative day. The bow-tie adjustable suture technique is a simple and effective approach for managing overcorrection in patients with intermittent exotropia. Adjusting the sutures on the sixth postoperative day can reduce the overcorrection rate and is considered a safe and effective method.

[Femtosecond laser-assisted open astigmatic keratotomy versus non-open astigmatic keratotomy for astigmatism correction in cataract surgery].

Objective: To compare the effects of femtosecond laser-assisted astigmatic keratotomy (FSAK) with and without a manual opening for correction of low to moderate corneal astigmatism at the time of cataract surgery. Methods: It was a prospective cohort study. Patients undergoing cataract surgery from June 2021 to June 2022 at the Army Specialty Medical Center were consecutively enrolled. To correct low to moderate astigmatism, they had combined FSAK with the corneal epithelium manually opened or not according to their own decisions. Pentacam HR corneal topography was performed at 3 months after surgery. The main indicators were target induced astigmatism, surgically induced astigmatism, difference vector, correction index and angle of error. The independent samples t-test was used for continuous variables conforming to a normal distribution, the Mann-Whitney U-test for those not conforming to a normal distribution, and the Chi-square test for categorical variables. Results: There were 51 patients (61 eyes), including 27 patients (31 eyes) receiving combined open FSAK and 24 patients (30 eyes) with non-open keratotomy. No statistical difference was found between the two groups of patients in terms of age, gender and mean follow-up time (P>0.05). The target induced astigmatism was 1.10(0.80, 1.50) D in patients with open keratotomy and 1.30(0.98, 1.73) D in patients with non-open keratotomy (Z=1.729, P=0.084). The surgically induced astigmatism was 0.70 (0.59, 1.25) D and 0.42 (0.20, 0.66) D (Z=-3.571, P<0.001), the difference vector was (0.51±0.31) D and (1.21±0.44) D (t=-7.238, P<0.001), the correction index was 0.78±0.32 and 0.38±0.25 (t=5.386, P<0.001), and the angle of error was -1.08°±10.76° and 5.93°±46.98° (t=0.809, P=0.422) in the two groups, respectively. Conclusion: Open FSAK can achieve better astigmatism correction and less postoperative residual astigmatism than non-open FSAK in cataract surgery.

[Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma].

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

[Short-term outcomes of prism treatment in a manner of reducing prism diopters step by step for small-angle acute acquired concomitant esotropia].

Objective: To investigate the short-term efficacy of the prism treatment in a manner of reducing prism diopters step by step for small-angle acute acquired concomitant esotropia (AACE). Methods: Retrospective case series study. The clinical data of 17 AACE patients with strabismus ≤25 prism degrees (PD) including 6 males and 11 females, aged 14 to 60 years, who underwent the prism treatment in the Strabismus and Pediatric Ophthalmology Clinic of Shanxi Eye Hospital from October 2018 to June 2020 were collected. The prism treatment was conducted by a step-by-step reduction of prism diopters. An under-corrected prism was applied to the patient for the first time, and the degree of the prism was reduced gradually with the decrease in the degree of strabismus. Statistical analysis was performed after 6 months of treatment. The treatment success was defined as obtaining orthotropia and deleting diplopia when prism glasses were weaned off. The strabismus degree, Worth 4 dot test results, near stereopsis (Titmus stereopsis) and synoptophore fusion function before and after treatment were compared, and the factors affecting the curative effect were analyzed. Statistical methods mainly included paired t-test, Wilcoxon rank sum test, the Fisher exact test and univariate logistic regression analysis. Results: Among these 17 patients, 15 had myopia and 2 had emmetropia. Pretherapeutic esodeviation was (13.94±5.83) PD at near (33 cm), and was (15.76±5.24) PD at distance (6 m). After 6 months of treatment, 7 patients were successfully cured. The deviation angle at distance [(10.60±7.16) PD] and near [(9.80±6.00) PD] of the remaining 10 patients at 6 months after prismatic treatment was significantly smaller than that before treatment [(17.50±5.40) PD and (16.10±5.47) PD; t=3.69, 4.10; both P<0.01]. The Titmus stereogram showed that 2 cases had no stereopsis, 6 cases had peripheral stereopsis, 3 cases had macular stereopsis, and 6 cases had foveal stereopsis before treatment. Stereopsis was significantly improved at 6 months after prismatic treatment, with 3 cases havimg macular stereopsis and 14 cases having foveal stereopsis (Z=-2.99; P<0.01). The Worth-4-dot test disclosed that, the number of patients who saw four lamps at distance and near was 0 and 2 before treatment, and 7 and 9 after treatment, respectively, and the difference was statistically significant (both P<0.05). The divergent fusional amplitude and convergent fusional amplitude in the synoptophore at 6 month after treatment was not significantly different from that before treatment (both P>0.05). The efficacy of treatment was not significantly related to the duration from onset to treatment, the pretherapeutic esodeviation, the Titmus stereoacuity, cycloplegic refractive error, and age (all P>0.05). None of the 7 patients, who were successfully cured had a recurrence of esotropia or diplopia during the observation period of 6 to 24 months (median, 11 months). Conclusions: Prism treatment in a manner of step-by-step reduction of prism diopters can significantly diminish the degree of esotropia and improve the binocular function in small-angle AACE. Furthermore, some patients could be cured, achieving orthophoria without diplopia.

[Clinical characteristics of patients with acute pulmonary embolism in high altitude area of Yunnan province in China].

Objective: To analyze the clinical features of patients with acute pulmonary embolism (APE) living in high altitude area of Yunnan province. Methods: This was a cross-sectional retrospective study. APE patients, hospitalized in our hospital between January 2017 and December 2019, were included. The selected patients were divided into low-risk group, medium-risk group and high-risk group according to risk stratification. The clinical data of patients, including demographic data, the main symptoms, risk factors of APE, heart rate and systolic blood pressure and laboratory testing results (D-dimer, cardiac troponin I (cTNI), N terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography and electrocardiogram examination results, were obtained through the electronic medical record system. The clinical characteristics of selected patients were analyzed. Results: A total of 392 patients, aged (63.5±15.7) years, 224 males (57.14%), were included in this study and there were 59 low-risk, 304 medium-risk and 29 high-risk patients in this cohort. The main clinical manifestations were chest pain (157(40.05%)), dyspnea (107(27.30%)), hemoptysis (55(14.03%)), syncope as the first symptom (20(5.10%)), and only 6 cases (1.53%) presented with the typical "Virchow's triad". Most of the patients were accompanied by atypical chest tightness (223(56.89%)) and cough (208(53.06%)). The main risk factors were venous thrombosis of lower limbs (179(45.66%)), hypertension (138(35.20%)), surgery (63(16.07%)), and chronic obstructive pulmonary disease (COPD) (62(15.82%)). There were 57 cases (14.54%) of coronary heart disease, 57 cases (14.54%) of diabetes, 51 cases (13.01%) of cerebral infarction, 47 cases (12.00%) of advanced age, 15 cases (3.83%) of tumor, 7 cases (1.79%) of activity restriction, 6 cases (1.53%) of pregnancy and 4 cases (1.02%) of hormone use in this cohort. The proportion of lower extremity venous thrombosis was significantly higher in low-risk group than in medium-risk group (P<0.01), COPD was more common in high-risk and medium-risk groups than in low-risk group (P<0.01), hypertension was more common in high-risk group than in medium-and low-risk groups (P<0.01). The proportion of advanced age was significantly higher in medium-risk group than in low-risk group (P<0.01). There were no significant differences in RBC and hemoglobin level between low-, medium-and high-risk groups (P>0.05). The level of D-dimer was significantly higher in high-risk group than in medium-and low-risk groups (P<0.05). Levels of NT-proBNP and cTNI were significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). Increased proportion of cTNI and NT-proBNP was significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). There were 105 (26.79%) patients with pulmonary hypertension (PAH). The incidence of PAH was significantly higher in high-risk group than in low-risk group (P<0.01). There were 104 patients (26.53%) with right ventricular enlargement, and the incidence of right ventricular enlargement was significantly higher in high-risk group than in medium-and low-risk groups (P<0.01). Characteristic changes of electrocardiogram in patient with APE were T-wave inversion of limb leads (98(25.00%)), followed by SⅠQⅢTⅢ (83(21.17%)). Conclusions: The main clinical manifestations of APE in Yunnan high altitude area are chest pain and dyspnea, and syncope is the first symptom in some patients, but the typical "Virchow's triad" is rare. The most common risk factors are lower extremity venous thrombosis, hypertension, and COPD. Clinical symptoms, risk factors and laboratory examination results differ among patients with different risk stratification.

[Association between education and the onset of disability in activities of daily living in middle-aged and older Chinese adults: The mediator role of social participation].

OBJECTIVE: To investigate the association between educational attainment and the onset of disability in activities of daily living (ADL), and to explore the mediating effect of social participation on such association. METHODS: A longitudinal dataset was drawn from the China Health and Retirement Longitudinal Study (CHARLS, 2015 to 2018). The measurements of educational attainment, social participation and other covariates were identified from 2015, while the outcome measurement of ADL disability was constructed with data from survey 2018. Descriptive analyses were conducted, and basic characteristics and social engagement of the respondents were compared between illiterates and non-illite-rates using Chi-square test. Logistic regression was used to investigate the associations of educational attainment and social participation on the onset of ADL disability. Mediation analysis was employed to examine the mediator role of the social participation on the linkage from being illiterate to the ADL disability onset. RESULTS: A total of 11 359 adults aged 45 years and above were included in the sample, of whom 3 222 were illiterates. The incidence of the onset of ADL disability of illiterates and non-illiterates were 10.4% and 6.2%, respectively. Among these respondents, only half of them were involved in social activities. Of all the 8 social activities, the percentage of interacting with friends (34. 1%) was the highest, and the lowest percentage was observed in participating in an educational or training course (0.6%). Moreover, the percentages of participation in all these 8 social activities among illiterates were significantly lower than that of their educated counterparts (all P < 0.001). The illiterate middle-aged and older adults were less likely to develop ADL disability in the follow-up period [adjusted odds ratio (aOR)=1.22, 95%CI: 1.02-1.45], and social participation was significantly associated with ADL disability onset (aOR=0.73, 95%CI: 0.63-0.85). Findings from mediation analysis illustrated that social participation accounted for 12.22% of the adverse effect of being illiterate on ADL disability onset. CONCLUSION: Social participation could buffer the negative effect of being illiterate on ADL disability onset in middle-aged and older adults, suggesting that engagement in social activities might have impact on prevention of impairments in physical function, especially for middle-aged and older illiterates.

[Long-term clinical effects of the bilateral superior oblique tendon suture spacer in the treatment of A-pattern strabismus].

Objective: To investigate the long-term clinical efficacy and safety of the bilateral superior oblique tendon suture spacer in treatment of A-pattern strabismus with superior oblique overaction (SOOA). Methods: Retrospective case series study. Twenty-one A-pattern strabismus patients who received the quantitative bilateral superior oblique tendon suture spacer with a complete follow-up from January 2009 to August 2017 were enrolled. Among these patients, 19 were exotropic and 2 were esotropic, including 11 males and 10 females, aged (14±9) years. Patients with unilateral superior oblique overaction, Broun syndrome or Helveston syndrome were excluded. The A-pattern strabismus, objective torsion, function of the superior oblique muscle and binocular vision were examined pre-and post-operatively. Paired t-test was used for normal distribution data, Wilcoxon rank-sum test was used for non-normal distribution data, Spearman rank correlation test and simple linear regression were used to analyze the correlation between the two variables. Results: The follow-up was 12 to 109 months (mean, 26±17 months). Twenty patients showed good alignment in the primary position with a deviation angle less than 10 prism diopter (PD), and 1 patient with esotropia had an angle greater than 15 PD. All the patients had no A pattern after surgery. The average pre-and post-operative A-patterns were (23.81±9.47) PD and (0.90±3.59) PD (t=11.29, P<0.01), respectively, and the average corrected A pattern was (23.52±9.68) PD.The average pre-and post-operative torsion was 3.18°±3.26° and -4.81°±4.13° (t=8.87, P<0.01), espectively, and the average corrected torsion was 7.95°±3.88°. No patient complained of torsional diplopia after surgery. The average amount of pre-and post-operative SOOA was 3.0 (2.0) and 0.0 (1.0) in 42 eyes (Z=-5.78, P<0.01), respectively. Suture extension of the superior oblique tendon was related with the pre-operative SOOA (r=0.47, P<0.01), but was not related with the pre-operative torsion (r=0.02, P=0.88). The linear regression results was suture extension=2.71× the grade of pre-operative SOOA (t=27.93, P<0.01). Conclusions: The bilateral superior oblique tendon suture spacer can improve the A-pattern, objective torsion and SOOA, with no torsional diplopia or V pattern after the long-term follow-up. It is a safe and effective superior oblique muscle weakening procedure. (Chin J Ophthalmol, 2020, 56: 853-858).

Superconductivity in HfTe5 across weak to strong topological insulator transition induced via pressures.

Recently, theoretical studies show that layered HfTe5 is at the boundary of weak &strong topological insulator (TI) and might crossover to a Dirac semimetal state by changing lattice parameters. The topological properties of 3D stacked HfTe5 are expected hence to be sensitive to pressures tuning. Here, we report pressure induced phase evolution in both electronic &crystal structures for HfTe5 with a culmination of pressure induced superconductivity. Our experiments indicated that the temperature for anomaly resistance peak (Tp) due to Lifshitz transition decreases first before climbs up to a maximum with pressure while the Tp minimum corresponds to the transition from a weak TI to strong TI. The HfTe5 crystal becomes superconductive above ~5.5 GPa where the Tp reaches maximum. The highest superconducting transition temperature (Tc) around 5 K was achieved at 20 GPa. Crystal structure studies indicate that HfTe5 transforms from a Cmcm phase across a monoclinic C2/m phase then to a P-1 phase with increasing pressure. Based on transport, structure studies a comprehensive phase diagram of HfTe5 is constructed as function of pressure. The work provides valuable experimental insights into the evolution on how to proceed from a weak TI precursor across a strong TI to superconductors.

Amino acid composition of royal jelly harvested at different times after larval transfer.

The amino acids in royal jelly (RJ) have a wide range of pharmacological and health-promoting functions in humans. Multiple studies on the amino acid quality and composition in RJ have investigated RJ harvested at 72 h after larval transfer. In contrast, the concentration of amino acids in RJ harvested before 72 h remains unknown. In this study, the concentration of free amino acids (FAAs) and total amino acids (TAAs) in RJ harvested at 13 time points between 24 and 72 h after transfer of ten Apis mellifera colonies were measured. Our results indicated that the most abundant FAAs were Pro, Phe, Lys, Glu, and Tyr, whereas the most abundant TAAs were Asp, Glu, Leu, Lys, and Val. The total FAA concentration in RJ increased with increasing harvest time, from 4.30 mg/g at 24 h to 9.48 mg/g at 72 h. In contrast, the variation in concentration of TAAs observed was a decrease-increase-decrease trend with 40 h (149.53 mg/g) and 52 h (169.62 mg/g) as inflection points. The highest and lowest concentrations of TAA were 197.96 and 121.32 mg/g at 24 and 72 h, respectively. To our knowledge, this is the first study to investigate the concentration changes of FAAs and TAAs prior to 72 h after transfer. Our results will provide theoretical support to guide production practices of beekeeping, as well as elucidate the relationship between the harvest time point and RJ content.

[Effects of pretreatment with dimethyloxalylglycine on the survival of multi-territory perforator flap in rat and related mechanism].

OBJECTIVE: To observe the effects of pretreatment with dimethyloxalylglycine (DMOG) on the survival of multi-territory perforator flap and the vessels of choke zone (CZ) 2 in rat, and to explore related mechanism. METHODS: Sixty adult SD rats were divided into group DMOG and normal saline group (NS) according to the random number table, with 30 rats in each group. Perforator flap with three angiosomes was made on the right dorsal side of rat, including deep iliac circumflex artery perforator, intercostal artery perforator, thoracodorsal artery perforator, as well as CZ 1 and CZ 2. Rats in group DMOG were intraperitoneally injected with 2 mL NS containing DMOG (40 mg/kg) 2 days before operation, 2 hours before operation, and 2 days after operation. Rats in group NS were intraperitoneally injected with equivalent volume of NS at the same time point. On post operation day (POD) 7, gross observation was conducted, and the survival rate of flap was calculated. On POD 7, the vascularity in CZ 2 and potential zone of flap was observed using angiography. On POD 7, new vessel in CZ 2 of flap was observed with HE staining, and the microvessel density (MVD) was calculated. On POD 7, the expression of vascular endothelial growth factor (VEGF) in CZ 2 of flap was detected by immunohistochemistry and Western blotting (respectively denoted as integral absorbance values and ratio of gray value), and blood flow volume of vessel in CZ 2 of flap was examined by laser Doppler perfusion imager. The sample number of each index was 6 in each group. Data were processed with t test. RESULTS: (1) On POD 7, rats in two groups all survived, and the flaps were not infected. In group DMOG, the necrotic area of flaps of rats with dark yellow crust and soft texture was observed approximately at the distal end of skin entry point of thoracodorsal artery perforator. In group NS, the necrotic area of flaps of rats with brownish black crust and hard texture was observed approximately at the distal end of CZ 2. The survival rate of flap of rats in group DMOG was (88±3) %, which was significantly higher than that in group NS [(82±3) %, t=3.38, P<0.01]. (2) On POD 7, there were clear vascular structure and many new vessels in CZ 2 of flaps of rats in group DMOG, with intact vascular structure in potential zone. On POD 7, there were unclear vascular structure and few new vessels in CZ 2 of flaps of rats in group NS, with disorder vascular structure in potential zone. (3) On POD 7, MVD in CZ 2 of flaps in rats of group DMOG was (29.2±2.2)/mm(2,) which was significantly higher than that of group NS [(20.3±3.6)/mm(2,) t=5.10, P<0.01]. (4) On POD 7, the expressions of VEGF in CZ 2 of flaps in rats of group DMOG detected by immunohistochemistry and Western blotting were 5 060±432 and 0.48±0.04 respectively, which were significantly higher than those of group NS (2 811±382 and 0.26±0.06, with t values respectively 9.54 and 5.67, P values below 0.01). (5) On POD 7, blood flow volume of vessel in CZ 2 of flaps in rats of group DMOG was (58±4) perfusion units (PU), which was significantly more than that of group NS [(46±4) PU, t=5.20, P<0.01]. CONCLUSIONS: DMOG can increase the survival rate of multi-territory perforator flap through promoting angiogenesis in CZ 2 of flap on the back of rat and improving blood supply of flap.

Development of a NanoString assay to detect leukemogenic fusion transcripts in acute myeloid leukemia.

INTRODUCTION: Detection of leukemogenic fusion transcripts in acute myeloid leukemia (AML) is critical for AML diagnosis. NanoString nCounter system is a novel probe-based gene expression platform capable of measuring up to 800 targets with advantages of reproducibility, accuracy, and sample type flexibility. To study the potential application of NanoString in leukemia at clinic, we used this technology to detect AML leukemogenic fusion transcripts and compared the performances with clinical molecular assays. METHODS: We developed a NanoString assay to detect seven leukemogenic fusion transcripts, namely RUNX1-RUNX1T1 (e5e12), PML-RARA (bcr1, bcr2, and bcr3), and CBFB-MYH11 (e5e12, e5e8, and e5e7). We set up the cut-off value for each fusion transcript and tested 42 de novo AML samples. We compared the results with reverse transcriptase-polymerase chain reaction (RT-PCR) and TaqMan reverse quantitative-polymerase chain reaction (RQ-PCR), the molecular methods standardly used at clinic. RESULTS: We demonstrated that the NanoString and RT-PCR results correlate well (P < 0.0001) and are highly concordant (95.2%). Using TaqMan RQ-PCR as a validation method and gold standard, we demonstrated superior accuracy and sensitivity of NanoString compared to RT-PCR and comparable specificity. Furthermore, we showed that NanoString is not as sensitive as TaqMan RQ-PCR in detecting very low level of fusion transcripts. CONCLUSIONS: NanoString can serve as a reliable and alternative molecular method to multiplexed RT-PCR for diagnosis of de novo AML with the perspective of screening/quantitation of a large number of leukemogenic fusion transcripts and prognostic genes. However, NanoString may not be an alternative method for monitoring minimal residual disease in AML.

[Association between ß-arrestin2 genetic polymorphism and response to methadone maintenance treatment in heroin-dependent patients in Han population in Hunan province].

OBJECTIVE: To study the distributions of three single nucleotide polymorphisms (SNPs) in ß-arrestin2 (ARRB2) which including rs3786047, rs1045280 and rs2036657 and to elucidate the relationship between these SNPs and response to methadone maintenance treatment (MMT) among heroin-dependent patients of Han ethnicity population in Hunan. METHODS: Han MMT patients were recruited in four random-chosen MMT clinics from Hunan province. Demographics, history of drug-use and MMT were recorded. ARRB2 SNPs were genotyped to determine the association between SNPs and response to MMT. RESULTS: Distributions of the three SNPs were in Hardy-Weinberg equilibrium in both groups (responders vs. non-responders). There was no statistical significance in the distribution frequency of genotype on rs3786047 (χ(2)=0.486 2, P=0.784), rs1045280 (χ(2)=1.591 9, P=0.451) and rs2036657 (χ(2)=1.061 5, P=0.588) in ARRB2 among the responders or the non-responders. CONCLUSION: Associations between the ARRB2 genotypes, rs3786047, rs1045280 and rs2036657, and MMT response in Han MMT patients in Hunan province did not appear.

[Molecular diagnosis of two Chinese cystic fibrosis children and literature review].

OBJECTIVE: To investigate the clinical manifestations and molecular features of cystic fibrosis in Chinese children. METHOD: A retrospective analysis of two pediatric cystic fibrosis cases diagnosed by gene test in Beijing Children's Hospital, Capital Medical University from 2010 to 2015, and Chinese cystic fibrosis reported patients searched of"cystic fibrosis, Chinese"on Chinese databases (CNKI, Wanfang Data) and PubMed from 1975 to 2015.The clinical manifestations and molecular features were analyzed. RESULT: One of the two newly diagnosed cystic fibrosis cases was a 10-year old girl who suffered from reccurent cough with expectoration and associated with cirrhosis.Sweat tests showed increased chloride twice with the lower level of 306.82 mmol/L.The other was an 8-month old boy with reccurent pneumonia from neonate, failure to thrive and fatty diarrhea.Two children had various degrees of bronchiectasis and massive sticky secretion on the bronchoscopy.They had no family history and their parents had no consanguineous marriage.CFTR mutations of c. 595C>T and c. 2290C>T were found in gene tests.On the database, twenty-one reports involving thirty-six Chinese patients (16 males and 20 females) were retrieved.Together with this group of 2 cases, a total of 38 cases were involved.The age at diagnosis was 4 months to 28 years with a median age of 10 years.All patients had reccurent respiratory infections, twenty-seven cases (71%) had malnutrition, fifteen (39%)had chronic diarrhea, and 16 cases (42%) had other digestive manifestations, including jaundice (4 cases), hepatomegaly (11 cases), ascites (2 cases) and pancreatic atrophy (3 cases). Five cases had a positive family history and six cases had a suspicious family history.Consanguineous marriage was found in three families.Sweat test revealed elevated chloride (52-327 mmol/L) in 28 cases.Eight of the 16 patients who performed pancreatic exocrine function examination showed pancreatic insufficiency.Eighteen of the 20 patients described the image manifestation of bronchiectasis.The age at death of 13 patients(34%) was 4 months to 25 years with a median of 11 years.Twenty-nine rare CFTR mutations were found in 25 tested patients, and c. 1766+ 5G>T(5 cases), c.2083dupG and c. 2684G>A (3 cases) held the top three mutation patterns. CONCLUSION: Respiratory symptoms and bronchiectasis are the main manifestations of Chinese cystic fibrosis patients, although some of them may be associated with malnutrition, digestive symptoms and pancreatic insufficiency. CFTR mutations are various and rare in Caucasians.

[Expression and clinical significance of ELOVL6 gene in high-grade serous ovarian carcinoma].

OBJECTIVE: To investigate the expression of elongation of very long-chain fatty acids family member 6 (ELOVL6) in high-grade serous ovarian carcinoma (HSOC), and explore the correlation between its expression and clinical prognosis in these patients. METHODS: The expression of ELOVL6 at mRNA and protein levels were respectively detected by reverse transcription (RT)-PCR and immune histochemistry method in 12 cases with normal ovarian tissues and 172 cases with HSOC from primary tumor site, forty of which had paired peritoneal metastatic tissues. RESULTS: (1) The results tested by RT-PCR showed that ELOVL6 expression in normal ovarian tissue was 4.8±1.1, while 1.2±0.7 in primary tumors and 1.8±0.9 peritoneal metastatic sites in HSOC. Compared with normal ovarian tissue, the level of ELOVL6 mRNA was significantly lower in HSOC (P<0.05). There was no significant difference between primary and peritoneal metastatic sites in HSOC (P=0.610). It was shown that ELOVL6 protein localized in cytoplasm of ovarian cancer cell by immunostaining assay. (2) ELOVL6 expression was observed in all normal ovarian tissue, 70.2% of G1-G2 and 48.8% of G3 HSOC (P<0.05). ELOVL6 expression in drug-resistant group were significantly lower than that in non-resistant group (39.1% vs 65.0%, P<0.01). The median disease-free survival was 41 months in the ELOVL6-positive group and 39 months in ELOVL6-negative group (P>0.05). The total median survival was 52 months in ELOVL6-positive group and 44 months in ELOVL6-negative group (P>0.05). CONCLUSION: Low expression of ELOVL6 may correlate with the poor differentiation and drug resistance in HSOC.

Paclitaxel induces apoptosis in leukemia cells through a JNK activation-dependent pathway.

Paclitaxel (PTX) is a mitotic inhibitor widely used in chemotherapy for many types of cancers, including solid tumors and hematological malignancies. However, the molecular basis of the anti-proliferation activity of PTX is not fully understood. In this paper, we focused on the role of c-Jun N-terminal kinase (JNK) pathways in PTX-induced apoptosis and proliferation inhibition. The effects of PTX were examined in human leukemia cell lines and patients' chronic lymphocytic leukemia (CLL) cells in relation to mitochondrial events, apoptosis, and perturbation of JNK activation using flow cytometry, siRNA, mitochondrial membrane potential determination, and western blotting. Exposure of cells to PTX at concentrations ≥ 10 nM for 18 or 24 h resulted in a significant release of cytochrome c from mitochondria to the cytosol, cleavages of procaspase 3 and poly (ADP-ribose) polymerase (PARP), and JNK activation, leading to apoptosis. The pan-caspase inhibitor BOC-D-FMK blocked the PTX-induced apoptosis but had no effect on cytochrome c release, suggesting that cytochrome c had been released before caspase activation. Moreover, both pharmacological JNK inhibitors SP600125 and JNK siRNA dramatically blocked PTX-induced apoptosis, cytochrome c release, caspase 3, and PARP cleavage. These findings demonstrate that JNK activation plays a critical role in the induction of apoptosis mediated by PTX in human leukemia cell lines and CLL patient-derived primary cancer cells, and this event is upstream of cytochrome c release, caspase 3, and PARP cleavage.

Molecular cloning and evolutionary analysis of captive forest musk deer bitter taste receptor gene T2R16.

Sensing bitter tastes is crucial for most animals because it can prevent them from ingesting harmful food. This process is mainly mediated by the bitter taste receptors (T2R) that are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires. Marked variation in repertoire size has been noted among species. However, research on T2Rs is still limited and the mechanisms underlying the evolution of vertebrate T2Rs remain poorly understood. In the present study, we analyzed the structure and features of the protein encoded by the forest musk deer (Moschus berezovskii) T2R16 and submitted the gene sequence to NCBI GenBank. The results showed that the full coding DNA sequence (CDS) of musk deer T2R16 (GenBank accession No. KP677279) was 906 bp, encoding 301 amino acids, which contained ATG start codon and TGA stop codon, with a calculated molecular weight of 35.03 kDa and an isoelectric point of 9.56. The T2R16 protein receptor had seven conserved transmembrane regions. Hydrophobicity analysis showed that most amino acid residues in T2R16 protein were hydrophobic, and the grand average of hydrophobicity (GRAVY) was 0.657. Phylogenetic analysis based on this gene revealed that forest musk deer had the closest association with sheep (Ovis aries), as compared to cow (Bos taurus), Tursiops truncatus, and other species, whereas it was genetically farthest from humans (Homo sapiens). We hope these results would complement the existing data on T2R16 and encourage further research in this respect.

Risk factors for mortality in severe multiply injury patients with acute hypoxemic respiratory failure.

OBJECTIVE: To investigate the risk factors related to mortality in severe polytrauma patients with acute hypoxemic respiratory failure (AHRF). PATIENTS AND METHODS: From December 2011 to December 2014, we identified and intubated 524 traumatic AHRF patients in a level 1 trauma centers. Amongst those, we enrolled seventy-six severe traumatic AHRF patients with an injury severity score (ISS) over 16 and need for over 24 hour intra-tracheal mechanical ventilation for our study. Patients were followed daily to collect data about demographics, injury characteristic, diagnostic, treatment, respiratory parameters, major complications, duration of mechanical ventilation, length of stay, prevalence of major complications and 28-days mortality. RESULTS: Of the 76 patients in our study, 61 patients were male. Patients' ages were from 15 to 78 years old (43±17) and the predominant source of trauma was road traffic accidents. Before ventilation, patients had a mean PaO2/FiO2 ratio of 108±63, pH of 7.1±0.3, PaCO2 of 54±24 mmHg, respectively. The PaO2/FiO22 ratios were significantly improved by ventilation and the average duration of ventilation was 9.63±8.74 days. There were two peak dying times and the 28-days ICU mortality rate was 28.9%. Logistic regression analysis revealed the mortality rate to be significantly higher in patients with higher APACHE II scores (odds ratio: 1.60, p=0.002), shorter intervals between injury and admission (odds ratio: -0.91, p=0.03) and between admission and ventilation (odds ratio: -1.85, p=0.012), and lower pH (odds ratio: -0.692, p=0.044). The receiver operating characteristic (ROC) curves showed that best cut off points for mortality predictors were APACHE II scores greater than 25, time interval between injury and admission less than 2h, time interval between admission and ventilation less than 0.5h, and pH <7.16. CONCLUSIONS: Traumatic AHRF patients requiring ventilation support show a high rate of early mortality. Greater vigilance for high APACHE II score, short time interval between injury and ventilation, low pH in traumatic AHRF patients is required.

Variation of craniocervical junction volume as an effective parameter for basilar invagination treatment.

OBJECTIVE: The major pathological change in basilar invagination (BI) is represented in the decrease of craniocervical junction (CVJ) volume resulting from abnormal bone protrusion around the foramen magnum. The diagnosis and clinical evaluation of BI is mainly based on the clinical manifestations and radiographic measurements by means of calculation of the scan lines of CVJ in X-ray, CT and MRI. With the transoral decompression atlantoaxial reduction plate (TARP III) system, the decompression, reduction and fixation can be achieved to decompress and stabilize medulla spinalis change the position of the dens in CVJ, thus expand the CVJ relative volume, relieve the compression on medulla spinalis and the nerve injury. However, the correlation between the dens position change and the variation of CVJ has not been established previously. This study focused on the clinical significance of the variation of craniocervical junction (CVJ) volume caused by the dens position change for the treatment of BI. PATIENTS AND METHODS: We've performed an analysis of data from 62 BI patients admitted from January 2008 to May 2013, who were treated by TARP III system. The data include preoperative, postoperative JOA scores (Japanese Orthopaedic Association scores, 17 points method), preoperative and postoperative X-ray, thin-slice CT scan with three-dimensional reconstruction and MRI scan to measure the cervicomedullary angle (CMA). We have analyzed the preoperative and postoperative three-dimensional CT data by means of MIMICS 10.01 software system according to the Box volume (BV) method to determine the changes of CVJ volume resulting from preoperative and postoperative dens position change, assessed the correlation between the CVJ volume changes and the JOA scores with correlation between CMA change and the JOA scores. All data were analyzed by paired t-test and Pearson correlation analysis. RESULTS: In all 62 patients, JOA scores were recovered from preoperative 9.26 ± 1.66 to postoperative 13.02 ± 1.44, CMA change rate was 21%, and CVJ volume change rate was 36%. The CMA change rate and the JOA score recovery rat exhibited relevance, as Pearson's correlation coefficient was 0.46 (p < 0.005). The Pearson's correlation coefficient between CVJ volume change rate and JOA score recovery rate was 0.63 (p < 0.005), and the CVJ volume change rate was significantly different while compared with the correlation between CMA change rate and JOA score (p < 0.005). CONCLUSIONS: the CVJ volume change rate is a sensitive and reliable parameter for the evaluation of neurological function improvement in patients with BI. It can be used as a predictor to evaluate the postoperative neurological recovery.